1. Field of Use
The present invention relates to a method of stimulating or enhancing an ornithine-urea cycle activity in ruminant gut tissues to detoxify ammonia and increase local urea recycling to the rumen for microbial protein synthesis.
2. Description of the Background
Ruminants are hoofed, even-toed, usually homed animals of the subculture Ruminanthia, such as cattle, sheep, goats, deer and giraffes, which characteristically have a stomach divided into four compartments, the first being the rumen, and which chew a cud made up of regurgitated, partially digested food.
Ruminants exhibit a poor efficiency of converting dietary protein into milk or muscle protein partly from the extensive degradation of protein in the rumen which leads to the production and absorption of large amounts of ammonia with significant excretion of nitrogen in urine. See Reynolds, C. K. et al., J. Nutr. 121:994–1003 (1991)
In particular, ruminants that consume pasture forage, such as alfalfa hay and orchard grass hay, produce and absorb large amounts of ammonia due to the extensive metabolism of the dietary protein by rumen microbes. The absorbed ammonia is toxic to the gut tissues and pancreas, and also to peripheral tissues, such as the brain, reproductive tract and nervous system, if spill-over of the ammonia into the arterial blood occurs, i.e. peripheral hyperammonemia. The liver of such animals converts nearly all absorbed ammonia to urea, which is either excreted into the urine or recycled to the rumen for microbial protein synthesis. While urea has little or no nutritional value to monogastric mammals, ruminants are known to be able to utilize urea as a source of food protein. The known overall ornithine-urea cycle occurring in the liver of ureotelic animals is depicted in FIG. 2.
The partition of urea between urine and rumen is variable, with 20 to 80% of urea synthesis excreted into the urine, rather than recycled to the rumen. The loss of urea in urine represents a major loss of nitrogen to the ruminant, which in turn leads to significant contributions to environmental pollution. Unfortunately, to date, there is little knowledge of how blood urea recycling is regulated in animals generally. Although there are presently a few approaches to reducing N excretion in ruminants, each has notable drawbacks and often only limited success.
Specifically, approaches which have been considered or which are being tested to reduce nitrogen excretion and improve nitrogen efficiency in ruminants are: 1) feeding increasing amounts of undegradable protein to ruminants to limit production of ammonia in the rumen, 2) feeding protected amino acids to ruminants to limit the intake of total protein, 3) feeding high fermentable energy food to increase capture of ammonia in the rumen, 4) reducing the enzyme activity of specific rumen bacteria (e.g., Prevotella ssp) to inhibit the breakdown of peptides to free amino acids and, hence, to ammonia (inhibitors: 1-[(E)-2-(2-methyl-4-nitophenyl)diaz-1-lenyl] pyrrolidine-2-carboxylic acid and diphenyliodonium chloride), 5) feeding condensed tannins (natural plant diphenyliodonium products) which bind feed protein and protect them from rumen microbial breakdown, and 6) feeding Monensin® to increase capture of rumen ammonia and decrease nitrogen losses. Monensin® is an antibiotic produced by the bacteria Streptomeyes cinnamonensis, and is commonly used to increase the weight gain to food ratio in beef cattle. As noted above, however, all of these approaches have drawbacks and are of limited use.
For example, the feeding of undegradable protein and protected amino acids requires the use of additional feed protein and the cost of protected amino acids. The feeding of condensed tannins also results in hypertrophy of the ruminant gut tissues and losses of nitrogen if not used in ideal situations.
It has been observed in rats and weaned pigs that both the colon and intestines possess the necessary complement of enzymes and allosteric regulations for citrulline and urea synthesis-suggesting that gut tissues of these animals have an ability to detoxify absorbed ammonia. See Mouille, B. et al., Biochem. Biophys. Acta. 1427:401–407 (1999) (rat), and Bush J. A. et al., J. Nutr. 132:59–67 (2002) and Wu, G., Biochem. J. 312:717–723 (1995) (pigs). However, it has not yet been demonstrated whether ruminant gut tissues also possess the ability to synthesize urea from absorbed ammonia.
Thus, a need exists for a more generally effective methodology for increasing nitrogen efficiency in ruminants by enhancing local rumen tissue conversion of rumen ammonia to urea and its return to the rumen for microbial protein synthesis, if such is possible.